白细胞介素-17在口腔扁平苔藓病损组织的表达研究

目的检测白细胞介素（IL）-17在口腔扁平苔藓（OLP）病损局部组织的表达情况．初步探索Th17细胞在OLP发病过程中的作用。方法26例OLP活检组织和6例健康颊黏膜组织制成匀浆,ELISA测定IL-17浓度,应用BCA总蛋白检测方法测定总蛋白浓度．根据IL—17相对含量（pg／mg）=细胞因子（pg／ml）／总蛋白（mg／ml）,计算IL-17相对含量;应用免疫组化方法检测组织中IL-17表达的组织分布。结果在所有标本中均能检测出IL-17的表达．对IL-17相对含量结果进行非参数秩和检验,与对照组相比差异无统计学意义,IL-17阳性染色主要在固有层呈散在分布．在表皮不完整的糜烂处及上皮下疱处,阳性细胞明显增多,上皮内极少见阳性染色。高倍镜下IL-17阳性染色主要分布在胞浆,部分细胞的胞外间隙也可见弱阳性染色。结论IL-17在OLP病损组织中均有表达,但与对照组相比,其表达水平差异无统计学意义;IL-17在OLP中的作用仍需进一步探讨。     

IL-2、IL-1O在口腔扁平苔藓发病中的作用

目的：通过对口腔扁平苔藓（OLP）局部组织及外周血中IL-2、IL-10表达进行研究,进-步探讨OLP发病机制。方法：应用免疫组织化学SABC法检测30例OLP中IL-2、IL-10的表达数量及分布,同时用ELISA法检测外周血中IL-2、IL-10的含量。结果：①在病损组织中,OLP组中IL-2、IL-10表达显著高于对照组（P〈0．05）。IL-2主要分布在淋巴细胞浸润带,在基底膜附近较集中;IL-10主要分布在固有层,远离基底膜。②在外周血中,糜烂型OLP组IL-2、IL-10含量明显高于对照组和非糜烂型OLP组（P〈O．05）。结论：①根据IL-2、IL-10在OLP中表达和分布情况,提示IL-2、IL-10在OLP发病机制中参与了机体免疫的调节和介导作用。②外周血中IL-10高表达,提示糜烂型OLP患者全身的免疫反应参与了本病的形成或可能伴有全身免疫系统功能紊乱。     

口腔扁平苔藓凋亡相关基因的表达及意义

目的：探讨凋亡相关基因P53，Bcl-2,Fas,Fas-L的表达在口腔扁平苔藓（Oral Lichen Planus OLP)病变形成及发展中的作用。方法：采用免疫组化SABC法对28例OLP病损中凋亡调节蛋白P53，Bcl-2,Fas,Fas-L进行检测，并与正常口腔粘膜比较，结果：（1）P53蛋白在正常口腔粘膜中表达阴性，但可在OLP上皮基底细胞及部分棘细胞中表达。（2）Bcl-2蛋白在正常口腔粘膜及OLP病损上皮中表达很弱或阴性，但在OLP固有层浸润的淋巴细胞呈强阳性表达。（3）Fas和Fas-L在正常口腔粘膜及OLP病损上皮中表达差异不显著（P＞0．05），结论：口腔扁平苔藓病变的形成及发展部分归因于凋亡，P53和Bcl-2蛋白对OLP局部上皮病变及炎性细胞浸润的存在可能有一定作用。而Fas和Fas-L系统在OLP病变形成及发展中可能不起主要作用。     

转录因子RORγτ和FOXP3在口腔扁平苔藓病损组织中的表达及意义

目的:口腔扁平苔藓(oral lichen planus,OLP)是一种发生于口腔黏膜的T淋巴细胞介导的自身免疫性疾病。辅助性T细胞(helper T lymphocytes, Th)在OLP的发病过程中具有重要作用,本研究旨在进一步探索OLP患者局部病损组织中辅助性T细胞亚群Th17细胞和Treg细胞的作用。方法:纳入43例OLP患者和13例健康志愿者。采用实时定量PCR法检测局部病损组织中Th17和Treg细胞的特征性转录因子RORγτ和FOXP3的表达,采用GraphPad Prism 5 软件对其表达差异进行统计学分析。结果:OLP局部病损组织中转录因子RORγτ和FOXP3的表达显著高于正常黏膜组织,而且均与OLP的临床分型密切相关。萎缩糜烂型OLP组病损组织中RORγτ/FOXP3比值显著高于网状型OLP组和健康对照组,而网状型OLP组的RORγτ/FOXP3比值虽然高于对照组,但差异无显著性。结论:Th17细胞和Treg细胞均参与OLP的局部免疫反应;同时,Th17/Treg失衡也参与了重症型OLP的致病过程,且表现为Th17细胞优势。     

IL-17在乳牙根尖周病损组织中的表达

目的:检测IL-17在乳牙根尖周病损组织中的表达和分布,分析其在不同病理类型及炎症程度之间的关系,探讨其在乳牙慢性根尖周炎发病机制中的可能作用。方法:收集120例乳牙慢性根尖周病损组织行常规组织病理学检查,确定病理类型并按炎症细胞浸润程度分级;免疫组织化学法检测组织中IL-17的分布特点;ELISA法检测IL-17的蛋白表达量。结果:120例乳牙慢性根尖周病损组织中根尖周肉芽肿占65.8%,根尖周囊肿占18.4%,根尖周脓肿占15.8%。IL-17在3种病理类型中均有表达,主要表达于淋巴细胞、浆细胞。ELISA结果显示IL-17在不同病理类型组中的表达均低于正常对照组,在根尖肉芽肿组中的表达与炎症程度呈负相关。结论:IL-17在乳牙根尖周病损组织内广泛存在,随炎症程度加重表达逐渐降低,推测IL-17在乳牙慢性根尖周炎的病程进展中可能发挥一定的抑制作用。     

调节性T细胞和Th17细胞在OLP中的表达

目的：通过观察调节性T细胞（regulatory Tcells,Treg）和Thl7细胞（helper Tcells17,Th17）在口腔扁平苔藓（OLP）组织中的表达情况,探讨其在OLP发生发展过程中的变化。方法：应用免疫组织化学双标记技术检测35例OLP患者和19例对照组口腔黏膜组织中CD25＋Foxp3＋、CD4＋IL-17＋细胞的表达。结果：OLP组病损组织中有大量CD25＋Foxp3＋细胞浸润,较对照组显著增多,两者差异非常显著（P〈0．01）。CD4＋IL-17＋细胞在OLP组织中的表达较正常口腔黏膜组织有增加趋势,但差异无统计学意义（P〉0．05）。经进一步统计学分析,CD25＋Foxp3＋细胞和CD4＋IL-17＋细胞数量改变在OLP组织中表达呈正相关（P〈0．05）。结论：Treg细胞的数量在OLP组织中增多,Thl7细胞可能协同Treg细胞,在OLP发生发展过程中发挥了一定的作用。     

口腔扁平苔藓病损区B7抗原及CD28的表达及意义

目的 :探讨B7/CD2 8共刺激旁路在口腔扁平苔藓 (OLP)病损形成及发展中的作用。方法 :采用免疫组化方法对 46例OLP病损区B7抗原 (B7-1/CD80 ,B7-2 /CD86)及其配体CD2 8的表达情况进行检测 ,并与其局部病变、临床病程及病变类型相联系。结果 :①CD2 8阳性细胞见于所有OLP病损固有层淋巴细胞浸润带中 ,占总浸润细胞数的 45 % -80 %。②CD86低水平表达于正常口腔黏膜上皮及固有层的部分树突状细胞 ,但在不同病程及病变类型OLP病损中均有表达上调 (t =3 4.3 5 ,P <0 .0 1) ;CD86阳性细胞数在有基底层破坏的OLP病损中更多 ,差异有显著性 (t =2 .72 ,P <0 .0 5 )。③OLP病损中CD86阳性细胞与CD2 8阳性细胞之间存在数量上的正相关关系 (γ =0 .946,P <0 .0 1) ;④CD80 低水平表达于 80 .43 %的OLP病损上皮及邻近的结缔组织中 ,但在正常黏膜无表达。结论 :CD2 8-B7共刺激信号涉及OLP病损的形成及发展过程 ;其中 ,口腔黏膜上皮抗原呈递细胞上的CD86与存在于T细胞上的CD2 8分子间的结合及产生的效应 ,在OLP局部破坏性病损的形成中可能起重要作用 ,而CD80 则可能与OLP病损的慢性迁延状态有关。     

口腔扁平苔藓发病机制中T淋巴细胞作用及分布变化的研究进展

口腔扁平苔藓（OLP）是一种发生于口腔黏膜的慢性炎症性疾病,是最常见的口腔黏膜疾病之一。因其长期糜烂病损有恶变现象,WHO将其列入癌前状态。0LP的主要病理改变是基底细胞液化变性及上皮下淋巴细胞浸润,其发病机制尚未完全明确,大量研究证实,OLP是一种由T细胞介导的自身免疫性疾病。近年来,国内外各项相关研究显示,无论在0LP患者的外周血还是1：3腔局部病损均显示出不同于正常人的T淋巴细胞分布。本文就T淋巴细胞在OLP发病中的作用及其亚群分布变化研究作一综述。     

细胞凋亡相关蛋白Bcl-2对OLP病损区淋巴细胞聚集的影响

目的:探讨凋亡相关蛋白Bcl-2在口腔扁平苔藓(OLP)病变中的生物学行为及对OLP皮损中浸润淋巴细胞聚集、分布的影响,进一步了解OLP的发病机制。方法:采用免疫组织化学检测法,与正常口腔黏膜对照,观察分析25例OLP皮损中Bcl-2蛋白的表达水平及淋巴细胞聚集、分布。结果:OLP病损区T细胞中Bcl-2过度表达,固有层淋巴细胞异常克隆、聚集,浸润增加。结论:OLP病损区中T细胞高密度聚集可能是Bcl-2诱导的局部淋巴细胞过度增殖后关联反应。     

口腔扁平苔藓中RANTES和CCR1的表达及其与肥大细胞迁移的关系

口腔扁平苔藓(OLP)的固有层中常有T淋巴细胞和肥大细胞的浸润。研究表明，一些化学因子及其受体与炎症进展期间T细胞和肥大细胞的迁移和聚集有关，并且这些炎性细胞的积聚和局部活化还可能与上皮基底细胞的破坏存在直接的相关关系，但这些炎性细胞在OLP发病机制中的作     

Th1 cytokines in oral lichen planus

BACKGROUND: Cell-mediated immune responses in oral lichen planus (OLP) may be regulated by cytokines and their receptors. METHODS: In situ cytokine expression and in vitro cytokine secretion in OLP were determined by immunohistochemistry and ELISA. RESULTS: The majority of subepithelial and intraepithelial mononuclear cells in OLP were CD8+. In some cases, intraepithelial CD8+ cells were adjacent to degenerating keratinocytes. CD4+ cells were observed mainly in the deep lamina propria with occasional CD4+ cells close to basal keratinocytes. Mononuclear cells expressed IFN-gamma in the superficial lamina propria and TNF-alpha adjacent to basal keratinocytes. Basal keratinocytes expressed TNF-alpha as a continuous band. TNF R1 was expressed by mononuclear cells and basal and suprabasal keratinocytes. There was variable expression of TGF-beta1 in the subepithelial infiltrate while all intraepithelial mononuclear cells were TGF-beta1-. Keratinocytes in OLP stained weakly for TGF-beta1. Unstimulated OLP lesional T cells secreted IFN-gamma in vitro. TNF-alpha stimulation down-regulated IFN-gamma secretion and up-regulated TNF-alpha secretion. IL-4, IL-10 and TGF-beta1 secretion were not detected. CONCLUSIONS: These data suggest the development of a T helper 1 immune response that may promote CD8+ cytotoxic T-cell activity in OLP.     

Expression of lymphocyte function-associated antigen 3 in oral lichen planus

OBJECTIVE: The expression pattern of lymphocyte function-associated antigen 3 (LFA-3) in the buccal mucosa of oral lichen planus (OLP) patients was compared to that of healthy controls to investigate the possible role of LFA-3 in cell interactions within OLP lesions.
MATERIALS AND METHODS: Samples of buccal mucosa from 17 clinically healthy individuals and 17 OLP lesions were analysed. Expression of LFA-3, CD2, CD3 and CD 14 was visualized by an immunoperoxidase technique and assessed microscopically.
RESULTS: In healthy buccal mucosa LFA-3 was expressed on keratinocytes, Langerhans cells within the epithelium and on endothelial cells in the lamina propria. In OLP patients a similar pattern of LFA-3 staining was observed. In addition, cytoplasmic LFA-3, without accompanying surface staining, was seen on a subpopul-ation of macrophage-like cells. Substantial amounts of LFA-3 also appeared to be associated with non-cellular components of the extracellular matrix within the inflammatory infiltrate.
CONCLUSIONS: We have obtained evidence for a previously undescribed localization of LFA-3 within macro-phages, and have observed that expression of LFA-3 is apparently elevated within OLP lesions. LFA-3 may play an important role in the pathogenesis of OLP.     

不同临床类型OLP中STAT3的表达及意义

目的：研究不同临床类型的口腔扁平苔藓（OLP）中细胞信号传导和转录激活因子3（STAT3）的表达及意义。方法：采用免疫组织化学方法分别检测10例正常口腔黏膜组织,29例非糜烂型OLP、16例充血糜烂型OLP损害中STAT3的表达。结果：STAT3阳性表达分布于细胞质和细胞核内。正常口腔黏膜、非糜烂型OLP、糜烂型OLP上皮层中STAT3阳性表达率分别为30．00％（3/10）、75．86％（22/29）、93．75％（15/16）;固有层中分别为0％（0/10）、65．52％（19/29）、100．00％（16/16）;三种类型上皮层两两之间相比,差异有统计学意义（P＜0．05）;固有层两两之间相比,只有非糜烂型OLP和糜烂型OLP之间差异没有统计学意义（P＞0．05）。结论：STAT3与OLP上皮层的炎症进程密切相关,对STAT3表达的研究将有助于进一步探究OLP的发病机制和早期临床诊疗。     

Oral lesions of lupus erythematosus patients in relation to other chronic inflammatory oral diseases: an immunologic study

The nature and distribution of mononuclear cells in non-ulcerated oral lesions of discoid (DLE) and systemic lupus erythematosus (SLE), were investigated and compared to other chronic inflammatory oral diseases (lichen planus (LP), contact lesion (CL), unspecified inflammation (UI), geographic tongue (GT), and leukoplakia (LK). For this purpose an immunoperoxidase technique based on staining with monoclonal antibodies was employed. In most LE specimens examined infiltrating cells consisted predominantly of a mixture of T cells (Leu 3a+ and Leu 2a+) that were distributed in the lamina propria, the submucosa, and occasionally also in the epithelium. In general, only few B cells were detected while macrophages were more frequent. In all LE specimens examined beta 2-microglobulin expression was observed on a large proportion of cells including infiltrating mononuclear cells as well as resident keratinocytes. In addition, most infiltrating cells displayed MHC Class II antigens according to a pattern HLA-DR greater than DQ greater than DP. Interestingly, expression of Class II antigens was also observed on epithelial keratinocytes but was restricted to HLA-DR and -DP gene products (DR much greater than DP). HLA-DQ expression was never observed on keratinocytes. In most LE specimens studied a small proportion (less than 5%) of inflammatory cells had detectable interleukin-2 receptors (IL-2R) and/or transferrin receptors (transf-R). However, expression of transf-R was also observed on basal epithelial cells, being more pronounced in DLE than in SLE lesions. The above staining patterns observed in LE lesions, when compared to other chronic inflammatory oral lesions, did not disclose any striking differences that could support the specific diagnosis of LE. However, the findings of Class I and II MHC gene products on oral keratinocytes suggest an important accessory role for these cells in directing the migration of activated lymphoid cells in the epithelium in chronic inflammatory lesions of the oral mucosa.     

Oral lesions of lupus erythematosus patients in relation to other chronic inflammatory oral diseases: an immunologic study

Abstract – The nature and distribution of mononuclear cells in non-ulcerated oral lesions of discoid (DLE) and systemic lupus erythematosus (SLE), were investigated and compared to other chronic inflammatory oral diseases (lichen planus (LP), contact lesion (CL), unspecified inflammation (UI), geographic tongue (GT), and leukoplakia (LK). For this purpose an immunoperoxidase technique based on staining with monoclonal antibodies was employed. In most LE specimens examined infiltrating cells consisted predominantly of a mixture of T cells (Leu 3a⁺ and Leu 2a⁺) that were distributed in the lamina propria, the submucosa, and occasionally also in the epithelium. In general, only few B cells were detected while macrophages were more frequent. In all LE specimens examined β₂-microglobulin expression was observed on a large proportion of cells including infiltrating mononuclear cells as well as resident keratinocytes. In addition, most infiltrating cells displayed MHC Class II antigens according to a pattern HLA-DR>DQ>DP. Interestingly, expression of Class II antigens was also observed on epithelial keratinocytes but was restricted to HLA-DR and -DP gene products (DR> >DP). HLA-DQ expression was never observed on keratinocytes. In most LE specimens studied a small proportion (<5%) of inflammatory cells had detectable interleukin-2 receptors (IL-2R) and/or transferrin receptors (transf-R). However, expression of transf-R was also observed on basal epithelial cells, being more pronounced in DLE than in SLE lesions. The above staining patterns observed in LE lesions, when compared to other chronic inflammatory oral lesions, did not disclose any striking differences that could support the specific diagnosis of LE. However, the findings of Class I and II MHC gene products on oral keratinocytes suggest an important accessory role for these cells in directing the migration of activated lymphoid cells in the epithelium in chronic inflammatory lesions of the oral mucosa.     

Oral lichen planus may enhance the expression of Th17-associated cytokines in local lesions of chronic periodontitis

Objectives

This study aims to compare the expression levels of interleukin (IL)-17 and IL-23 in local periodontal tissues from patients with both chronic periodontitis and oral lichen planus (CP-OLP), patients with chronic periodontitis (CP) only, patients with oral lichen planus (OLP) only, and healthy controls (HC).

Materials and methods

The periodontal tissues were collected from 15 CP-OLP patients, 15 CP patients, 15 OLP patients, and 10 healthy controls. Immunohistochemistry (IHC) and real-time quantitative PCR (qPCR) was performed to investigate the protein and mRNA expression level of IL-17 and IL-23 in periodontal lesions from these four groups.

Results

IHC statistical analysis showed that the expression level of IL-17- and IL-23p19-positive cells significantly increased in CP-OLP group compared with that in CP (P?<?0.01) and OLP groups (P?<?0.05), showing intense staining reaction in local lamina propria lesions. Meanwhile, qPCR result showed higher IL-17 mRNA level in CP-OLP compared with that in CP and OLP groups and demonstrated a significant increase than OLP group (P?<?0.05). Moreover, it was found that IL-17 mRNA expression level in erosive CP-OLP patients was significantly correlated with probing depth and attachment loss (P?<?0.05).

Conclusions

This study indicated that there was an increased expression level of IL-17 and IL-23 in periodontal tissues from periodontitis patients with oral lichen planus, which might aggravate the inflammatory response in local lesions.

Clinical relevance

Oral lichen planus and chronic periodontitis may have interaction in disease pathogenesis, while IL-17 detection in local lesions may be helpful in identifying the disease severity in periodontitis patients with oral lichen planus.     

Activation of nuclear factor-kappa B correlates with tumor necrosis factor-alpha in oral lichen planus: a clinicopathologic study in atrophic-erosive and reticular form

Backgroud:  Nuclear factor-kappa B (NF-κB) is believed to be involved in the pathogenesis of various inflammatory diseases, including oral lichen planus (OLP). The objective of the present study was to investigate the possible relationship between NF-κB activation and expression of tumor necrosis factor-alpha (TNF-α) in OLP and their expression pattern in relation to several clinical features.
Methods:  Thirty OLP cases were divided into atrophic-erosive form (14 cases) and reticular form (16 cases) according to their clinical manifestations. The expression of NF-κB p65 and TNF-α of both two groups were investigated by immunohistochemical staining, and the percentage of positive cells was calculated in each case. Biopsies of 10 normal oral mucosa (NOM) also underwent the same procedure as controls.
Results:  Nuclear factor-kappa B p65 nuclear staining was found in nuclei of basal and suprabasal epithelial keratinocytes in OLP, however, no positive staining was found in NOM. Positive TNF-α staining was detected in cytoplasm of basal epithelial keratinocytes in OLP, and only scattered staining was detected in NOM. Expression of NF-κB p65 and TNF-α were significantly different with respect to clinical forms and lesion sites ( P  < 0.05), except for genders ( P  > 0.05) in 30 OLP cases. NF-κB nuclear staining positively correlated ( r  = 0.676, P  < 0.01) with TNF-α overexpression in OLP.
Conclusions:  Nuclear factor-kappa B activation and its correlation with overexpression of TNF-α may play an important role in pathogenesis of OLP. There might be a positive regulatory loop between NF-κB and TNF-α, which may contribute to inflammation in OLP; NF-κB may also protect epithelial keratinocytes from excessive apoptosis.